RESEARCH

Nanopore & NanoFluidic Device Fabrication

Left: cartoon representation of nanopore fabrication via CBD. Right: TEM images of two CBD-fabricated nanopores, one on a 20-nm thick membrane and the other on a 30-nm thick membrane locally thinned down to 10 nm.

We invented nanopore fabrication by controlled breakdown (CBD), a simple, rapid, and cost-effective method for creating individual solid-state nanopores directly in solution (e.g. 1M KCl pH8). Conventional transmission electron and focused ion beam pore drilling methods were slow, cumbersome, suffered from low yield, and required millions of dollars worth of clean room equipment. In contrast, our CBD method consists of simply applying an electric field across a solid-state membrane, with a strength that is at or near the dielectric breakdown strength of the membrane.  A tunneling current is monitored until a sharp increase indicates the spontaneous formation of a nanopore and the onset of ionic current. The pore size can be precisely enlarged by applying time-varying voltage waveforms. Compared to the equipment require for beam-based fabrication (TEM, FIB, HIM), CBD requires a simple circuit to source a voltage and monitor a current. The method can even be implemented with a 9V battery and a few off-the-shelf op-amps, capacitors and resistors.

Our revolutionary fabrication method possesses the following distinguishing attributes over other state-of-the-art fabrication techniques:

• Ultra-low cost: Price of equipment almost nil, a >10^6-fold reduction over beam-based methods.

• Precise pore sizing: Diameter of pore from 0.5-nm to 100-nm achieved with sub-nm precision.

• Fast and Efficient: Pore fabrication directly in salt solution in seconds to minutes, and ready for biosensing, eliminating lengthy post-processing steps of beam-fabricated nanopores.

• Versatility: Applicable to various materials (e.g. SiN, graphene), multilayered membranes (incl. metal-coated dielectrics) and diverse device architectures (e.g. microfluidics).

• Amenable to integration: pores can be fabricated in-situ, within embedded structures with no need for direct line-of-sight access, using similar electronics and electrodes to those employed in sensing applications.

So far, we have published 6 articles describing the principles of our CBD technology (#1#2#3#4, #5, #6) and filed 4 patent applications (2 of which are now issued).

Most recently we have published an article in Nature Protocols that presents our accumulated knowledge of nanopore fabrication by CBD since our initial publication of the method, and freely provide to the research community a software, plans for building the hardware and our latest protocols required to reliably automate fabrication of low noise, precisely sized, solid-state nanopores.

Our group is continuing to explore alternative fabrication strategies for making individual nanopores, fine tuning a pore size, and creating large nanopore arrays.

Fundamental of Molecular Capture and Passage through Nanopores

We study the fundamentals of the molecular capture and passage through nanopores. In addition to linear DNA polymers under various experimental conditions, we explore the transport properties nanostructured DNA (origami), and DNA-protein complexes. We also investigate how molecular conformation, as well as entropic and enthalpic forces, influence the dynamics of passage by creating advanced nanopore devices to manipulate individual molecules before capture.

Single-Molecule Counting with Nanopores

We are developing strategies and assays for rapidly and accurately counting single-molecules electrically with nanopores. We are also developing tools and methods for accurately extracting capture rate information and measuring molecular concentration from nanopore data.

Integrating Nanopores within Microfluidics

In collaboration with the team of Prof. Godin, we are developing various types of microfluidic devices to integrate different sample manipulation capabilities with nanopore sensing.

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